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Respiratory infect
Lectures 27-32
| Question | Answer |
|---|---|
| Anatomical characteristics of the URT | nasopharynx, larynx, and trachea has normal microflora, filters out particles, lined with mucociliary blanket and ciliated epithelial cells, normal temp 33C, IgA Ab |
| Characteristics of the LRT | bronchi, bronchiloes, alveoli normally sterile, bronchi and bronchioles lined with mucociliary blanket |
| Alveoli | no mucociliary blanket, no ciliated epithelial cells, normally sterile, only particles less than 5 microm can enter, lined with alveolar macrophages, IgG predominant, IgA present, damage interferes with gaseous exchange |
| Types of RT infections | professional/frank invaders: invade healthy RT secondary invaders: invade when damage/deficiency/loss of defenses already exists |
| Etiology of RT infections | extremely variable, affected by many host and microbial factors, single pathogen can be associated with many syndromes or many syndromes can be associated with a single pathogen |
| underlying mechanisms leading to a secondary RT infection | changes ro the RT: epithelial damage, airway function, up regulation and exposure of receptors Alteration of the innate immune response |
| role of normal microflora | protect by occupying receptors, producing antimicrobials |
| Normal microflora in URT that can be pathogenic | corynebacterium, enterobacteriaceae, haemophilus, moraxella, mycoplasma, staph, strep, neisseria, propionibacterium, treponema, candida |
| Other normal microflora in the URT | acinetobacter, actinobacillus, actinomyces, cardiobacteria, eikenella, eubacterium, fusobacterium, kingella, peptostreptococcus, prevotella, prophyromonas, stomatococcus, veillonella |
| exogenous infection | inhalation of droplets (talking, sneezing, coughing), inhalation of dust with fungal spores, self inoculation of eyes, nose, or mouth |
| endogenous infection | due to normal microflora, movement of flora to an unusual location (due to age, predisposing infection), preceding infection causes damage, aspiration of URT flora into unusual location |
| diagnosis of LRT infections (bacterial) | s. pneumoniae, h. influenzae, s. aureus, gram -:gram stain and culture legionella: culture, urine Ag, serology, PCR m and c pneumoniae: serology, culture, PCR bordetella: culture, DFA, serology, PCR mycobacteria: acid fast, culture |
| diagnosis of LRT infections (viral) | influenza: virus isolation respiratory syncitial virus: Ag detection HPIV 1-4: virus isolation adenovirus: Ag detection, PCR |
| serological tests | used for viruses or difficult to culture bacterial pathogens complement fixation, ELISA, latex agglutination |
| culture media | selective and differential used for elimination of normal flora and enable differentiation between bacterial species |
| specialized media | B. pertussis: bordet-gengou C. diptheriae: tinsdale agar, cysteini-tellurite agar |
| key respiratory pathogens | adenoviruses, rhinoviruses, coronaviruses, HPIV, respiratory syncytial viruses, influenzaviruses |
| Adenovirus | family adenoviridae,isocahedral capsids, non-enveloped,fibers on each penton vertices (have affinity for cell surface receptors and hemagglutinin properties), serotype specific Ag=virion surface, trigger neutralizing Ab, linear dsDNA, replicate in nucleus |
| Phases of viral transcription (adenovirus) | Early (E1-4) and late (L1-5) |
| E1A | responsible for modulation of cellular metabolism to increase viral replication. Promotes transformation, deregulates cell growth |
| E1B | cooperates with E1A and p53 to promote oncogenesis and transform via blockage of apoptosis |
| E2 | gene products=E2A and E2B. Necessary for replication of viral DNA, interact with variety of cellular factors |
| E3 | encodes for products that interfere with host defences, prevents TNF alpha and inflammation |
| E4 | facilitates virus messenger RNA metabolism, promotes virus DNA replication and shuttling off of host protein synthesis |
| L1-5 | required for virus production, structural components, encapsidation |
| Pathogenesis (adenovirus) | fiber enables attachment to host cell receptor, penton base inhibits cellular mRNA synthesis&causes cell rounding& tissue damage; interferes with MHC I expression (E3gp 19K binds to heavy chain of MHCI & prevents transport to cell surface), TNF, IFN a& b |
| epidemiology (adenovirus) | widespread, 75% before 14 yrs old, ocular respiratory or GI systems, transmission fecal oral mostly, but respiratory too |
| outcomes (adenovirus) | lytic infection, latent infection in lymphoid tissues |
| symptoms (adenovirus) | cold like: cough, runny nose, pharyngitis, fever, conjunctivitis, pneumonia, acute respiratory disease |
| differences in age groups (adenoviruses) | infants/young children: febrile, undifferentiated URTI children/adults: pharyngoconjunctival fever, follicular conjuntivitis, epidemic keratoconjunctivitis Military: acute respiratory disease young, military, immunocompromised: pneumonia |
| Rhinoviruses | family:picornaviridae, small, isocahedral, non-enveloped, ss+RNA, replicate in cytoplasm |
| Pathogenesis (rhinoviruses) | attachment to ICAM1 via surface canyon/clefts replicate and destroy ciliated epithelium of nasal and tracheal mucosa causes vascular engorgement, increased vascular permeability, increaed mucous production |
| epidemiology (rhinoviruses) | humans=only reservoir, more common and severe in young children, classification by specific neutralization with antisera, many siculating serotypes in one community, transmitted by hand contact, high in close contact environments |
| control (rhinoviruses) | difficult because of many serotypes and lack of cross reactivity therapy based on targeting virus or symptoms |
| coronaviruses | common cold (2nd most common), SARS, family coronaviridae, enveloped, helical nucleocapsid, surface fringe (glycoproteins), ss+ linear RNA, replicate in cytoplasm |
| Coronavirus S protein | spike protein, define tissue tropism, attach to proteins or carb receptors on host cell and enable fusion, Ab against S protein are neutralizing, helps with survival in GI tract |
| epidemiology (coronavirus) | isolated from human and animals, no cross infection, re-infection by same serotype possible, transmission by droplets (mostly) and some fecal oral |
| pthogenesis (coronavirus) | optimal replication in ciliated nasal epithelium, rest unclear because no good animal model |
| HPIV | laryngotracheobronchitis (croup), bronchitis, bronchiolitis, family paramyxoviridae, enveloped, glycoprotein with hemagglutinin & neuraminidase activity,fusion factor, ss- sense RNA, replicates in cytoplasm, fusion=release of nucleocapsid in cytoplasm |
| Fusion factor (F3) | enables fusion of virus and host cell membranes, Ab against F protein are neutralizing |
| HN activity | mediates infection by binding neuraminic acid containing molecule on host cell surface |
| pathogenesis (HPIV) | V proteins (fusion proteins) prevent apoptosis, alter cell cycle, inhibit double stranded RNA signaling, prevent interferon biosynthesis |
| Epidemiology (HPIV) | all age groups, range of respiratory syndromes from mild cold like to pneumonia |
| Respiratory syncytial virus (RSV) | family paramyxoviridae, enveloped, helical nucleocapsid, virally enclosed surface proteins, fusion factor (G glycoprotein: attachment), no glycoprotein with HN activity, ss- sense RNA, replicates in cytoplasm |
| epidemiology (RSV) | main cause of serious LRTI, main cause of hospitalization for RTI, main organism for bronchiolitis in children <1 yr (>81%), >50% pneumonia in children <1 yr, seasonal |
| pathogenesis (RSV) | entry via epithelium of nose and eye, self inoculation through droplets on hand, F&G proteins mediate attachment, replicate in nasopharyngeal epithelium, localized infection, no viremia |
| spread (RSV) | after 2-5 days spreads to LRT, causes bronchiolar epithelium necrosis, destruction of ciliated epithelial cells, infiltration of lymphocytes and mononuclear cells. Disesae enhanced when children are vaccinated using heat killed vaccine |
| Influenza | actue influenza, family orthomyxiviridae, division into A, B, and C based on nucleocapsid and matrix proteins, enveloped, helical nucleocapsid, 2 surface glycoproteins (H and N (not in C)), ss- segmented RNA, replicates in nucleus |
| subgrouping of influenza A | hemagglutinin and neuraminidase (see next 2 slides) |
| Hemagglutinin (influenza A) | rod/spike shaped, 25% of viral protection, major Ag against which neutralizing Ab directed, 4 subtypes (HA1-3, 5), requires cleavage to be active: carried out by cellular proteases in nucleus |
| Neuraminidase (influenza A) | mushroom like tetramer with slender stalk, sailidase enzyme:removes terminal sialic acid residues from glyoproteins& glycolipids. Enables release of budding virus from host cells, helps virus move through mucin layer for attachment. 2 subtypes |
| Influenza A | very severe, animal reservoir, pandemics, epidemics, antigenic shift and drift |
| Influenza B | Severe, no animal reservoir, no pandemics, epidemics, antigenic drift |
| Influenza C | mildly severe, no animal reservoir, no pandemics, no epidemics, antigenic drift |
| Pathogenesis (influenza) | attaches to sialyloligosaccharide, established primary infection in URT, NA cleaves mucus and allows attachment, replicates in columnar epithelial cells, HA mediates fusion via RME, mature virus released apically and spreads cell to cell |
| genetic variability | segmented RNA genome susceptible to mutation and can undergo recombination |
| Antigenic drift | can involve H or N Ag and genes encoding non-structural proteins, may be due to single mutation, selective pressures, frequently occurs in A (somtimes in B and C) |
| Antigenic shift | sudden, major change in H or N (>50% altered),causes epidemics/pandemics,due to genetic reassortment, can occur in animal reservoirs, new subtype, little/no immunity in population |
| treatment (influenza) | amantadine and rimantadine (prophylaxis for type A) olsetamivir (neuraminidase inhibitor, types A and B) prevention (trivalent vaccine: live attenuated, inactivated subvirion, or surface Ag) |
| Streptoccoci | gram+, non-motile, non-spore forming, catalast negative, fermetative metabolism, anaerobic, lipoteichoic acid and polysaccharide in cell wall, many virulence factors, cultured on blood agar, sensitive to optochin and bacitracin |
| streptoccocus pyogenes | pharyngitis, group A, beta hemolytic, bacitracin sensitive, optochin resistant. Causes scarlet fever, acute glomerulonephritis, rheumatic fever |
| epidemiology (pyogenes) | normal microflora in nasopharynx, main cause of bacterial pharyngitis in 2-20yr olds, droplet transmission, winter and early spring distribution |
| Streptococcus pneumoniae | pneumonia, sinusitis, otitis media, in adults: most common cause of bacterial pneumonia, lancet shaped, in pairs, alpha hemolytic, optochin sensitive, bacitracin sensitive |
| epidemiology (pneumoniae) | commonest cause of community acquired pneumonia, normal nasopharyngeal flora (carried by 5-70% of people), no animal/environmental reservoir |
| Pathogenesis (pneumoniae) | capsule important as virulence factor, sIgA protease, pneumolysin and autolysin, can take up DNA through transformation |
| pneumolysin | thiol activated pore forming toxin, binds to cholesterol, released following lysis of bacteria when exposed to autolysin. Inhibits ciliated epithelial cell activity, cytotoxic for alveolar and endothelial cells, causes inflammation, decreased PMN effect |
| autolysin | when activated breaks peptide cross linking of PG enabling pneumolysin release. Causes release of cell wall fragments, triggering an inflammatory response, contributes to pathogenesis |
| Prevention (pneumoniae) | Ab against capsule=protective polyvalent capsular polysaccharide vaccine, recommended for young/old, those with chronic disease, HIV,and alcoholics |
| Antibiotic resistance (pneumoniae) | penicillin usually drug of choice, resistance is due to alterations in PBP resulting in a reduced affinity for beta lactam antibiotics |
| Corynebacterium diptheriae | diptheria, gram+, pelomorphic rods, 4 biotypes, facultative anaerobe |
| epidemiology (diptheriae) | unusual in developed countries due to vaccine, less than 10 per year in US, endemic in some subtropical and tropical countries |
| pathogenesis (diptheriae) | non invasive organism does not enter blood stream, exotoxin is main virulence factor, inflammation and formation of a pseudomembrane, organ damage |
| lad identification (diptheriae) | culture (black shiny colonies on tinsdale agar: selective for K tellurite and differential for cystinase activity) and detection of toxin (PCR or Elek test: demonstrates toxin production). Both are necessary |
| Haemophilus influenzae | otitis media, pneumonia, epiglottitis, gram-, pleomorphic, facultative anaerobe, normal in URT flora, serotyped by capsule (a-f), type b associated with invasive disease, nontypable strain carried by 50-80% of people |
| epidemiology (influenzae) | sporadic, human pathogen, no animal/environmental reservoir, introduction of Hib vaccine has changed the profile of serotypes involved in disease |
| Pathogenesis (influenzae) | pili, non-pilus adhesins, LPS (impairs ciliary function), antiphagocytic capsule made of PRP, IgA proteases (more than 30) |
| lab identification (influenzae) | coagulase negative, catalast positive, chocolate agar or agar with X and V growth factors (X acts as hemin, V is NAD) |
| prevention (influenzae) | Hib vaccine, immunity correlated with Ab against PRP capsule, vaccine made of PRP coupled to a protein carrier, mediated T cell dependent response |
| Bortadella pertussis | pertussis, gram- coccobacillus, small |
| epidemiology (pertussis) | may be reemerging, typically occurs in unvaccinated kids and adults whose vaccines have waned, adults are important reservoir, highly communicable via aerosols, 90%of those exposed become infected |
| pathogenesis (pertussis) | bacterium is non-invasive, attaches to ciliated epithelia of bronchi and trachea via pili, Fha (agglutinates RBC, attaches to galactose N-acetylglucosamine residues of host cell glycolipids), and pertussis toxin. |
| toxins in pertussis | Pertussis toxin (ADP ribosylator, targets G proteins, PT), adenylate cyclase/hemolysins toxin (ACT), tracheal cytotoxin(TCT), lipooligosaccharide (LOS), dermonecrotic toxin (DNT) |
| phases of pertussis (whooping cough) | incubation: asymptomatic, 1 wk catarrhal: non-specific, 10d-2wk paroxysmal: characteristic signs (5-10 repeated coughs in 1 exhalation, staccato attacks, vomiting) convalescent |
| lab identification (pertussis) | nasopharyngeal swab or secretion (not cotton swab), culture (100% specific), chocolate agar with cephalosporin, PCR |
| prevention (pertussis) | DaPT vaccine (sP=acellular pertussis), whole cell vaccine (formalin inactivated), inactivated PT+acellular components (can decrease over time, booster shots necessary) |
| Kelbsiella pneumoniae | severe bronchopneumonia, chronic desrtuctive lung abscess, family enterobacteriaecae, gram-, non motile, large capsule (uronic and pyruvic acid), microbial flora (in 5% of healthy individuals), high affinity iron uptake systems (aerobactin&enterochelin) |
| Features of lung abscesses (klebsiella) | >1 area of lung parenchyma replaced by cavities filled with debris, usually polymicrobial, leads to rotting of lungs (putrid odor to breath and sputum), redcurrent jelly sputum |
| Legionella pneumophilia | legionaire's disease, pontiac fever, gram- rods, single polar flagellum, no capsule, maybe a slime layer |
| epidemiology (legionella) | in freshwater environments as parasite of free living amoebae, can be sequestered in biofilms, exposure by inhalation of bacilli in aerosols (air conditioning, showers), immunocompromised, elderly, males, smokers, & those with chronic bronchitis at risk |
| pathogenesis (legionella) | facultatively intracellular, uptake via phagocytosis, survival due to prevention of phagosome acidification and blocking phagosom-lysosome fusion, damage due to host inflammatory response, virulence factors |
| lab identification (legionella) | culture on BYCE or suitable agar, identification to genus level sufficient, demonstrate organisms or compounds, demonstrate significant levels of Ab |
| Mycobacterium tuberculosis | TB,large, acid fast, highly contagious, aerobic, has peptidoglycan, mycolic acids, and LAM |
| peptidoglycan (TB) | similar to gram+ bacteria, NAM and NAG cross linked via L-alanyl-D-isoglutamiyinyl meso-diaminopimelyl D-alanine tetrapeptides |
| Mycolic acids (TB) | high moecular weight, make 60% of cell weight, slow growth and formation of clumps and cords, resist detergents, hydrophobic, extend survival |
| LAM (TB) | similar to O Ag LPS, induces cytokine production by macrophages, suppresses T cell proliferation, inhibits IFN gamma activation of macrophages, interacts with dendritic cells to enable uptake and entry |
| Epidemiology (TB) | 1/3 to 1/2 of worlds population carries latent infection, many are HIV related, minimum infective dose=10 bacilli, risk elevated by defects in cell mediated immunity, HIV patients have shorter duration between infection and disease |
| pathogenesis (TB) | intrcellular survival in alveolar macrophages, prevent oxidative burst& inhibit phagosome-lysosome fusion (sulfolipids), resist lysosomal enzymes& ROI (cell wall lipid, LAM, superoxide dismutase),escape into cytoplasm, iron acquisition through siderophore |
| lab identification (TB) | culture on lowenstein-Jensen agar or olein acid, Zeihl-Neesen stain, PPD: intradermal injection, measure diameter (>5: HIV, >10: healthcareworkers,those in institutions, >15:everyone) |
| Prevention (TB) | prophylactic antimycotics after exposure, reduce overcrowding and poverty, BCG vaccination |
| Primary fungal pathogens-shared features | acquired by inhalation of soil and decaying organic matter, frequently asymptomatic or mild, endemic to certain geographical areas, clinical presentation depends on level of exposure and immunologic status, dimorphic |
| pathogenesis of endemic mycoses | inhaled-->reach terminal bronchi-->convert to form capable of replication-->colonize respiratory mucosa components of cell wall may be important |
| diagnosis of fungal pathogens | sputum, BAL, transtracheal aspirate, lung biopsy, direct microscopy, culture on appropriate media, nucleic acid probes, fixed specimens, delayed hypersensitivity skin tests (coccidiodin-mycelial phase Ag, Spherulin-spherule phase Ag), exoantigen test |
| Histoplasma Capsulatum | histoplasmosis, primary pathogen, 2 significant varieties (capsulatum and duboisii) |
| capsulatum capsulatum | pulmonary and disseminated, infections, eastern US Mexico central and South America, thinner cell walls, smaller size |
| capsulatum duboisii | skin and bone lesions, tropical Africa, thicker walled, larger yeasts |
| epidemiology (histoplasma) | natural habitat: saphrophyte in most rich soils with high N2 content (bird/bat feces), old decaying buildings, areas of demolition or reconstruction |
| pathogenesis (histoplasma) | facultative intracellular pathogen in monocyte (survival=pH mod),infection by inhalation,can disseminate via liver, spleen,contained by cell mediated immune response,can detect using skin DTHR, persistent subclinical infection with subsequent reactivation |
| Blastomyces dermatidis | primary pathogen, blastomycosis, mycelium: branching, septate; yeasts:oval to round |
| epidemiology (blastomyces) | similar geographic distribution to histoplasmosis, infection due to inhalation of condida and hyphal fragments, leads to cutaneous infection (primary or secondary), or systemic infection (sublcinical, acute primary pulmonary, chronic pneumonia, systemic) |
| Coccidiodes | coccidioidomycosis |
| epidemiology (coccidioidomycosis) | exposure through inhalation of hyphal arthroconidia, in arid and semi-arid soils, highest exposure in late summer/early fall and in dry seasons preceded by rainfall. California (immitis) other places (posadasii) |
| pathogenesis (coccidioidomycosis) | inhalation of arthroconidia-->primary coccidioidomycosis, convert to large spherule (size prevents phagocytosis), filled with endospores |
| outcomes (coccidioidomycosis) | asymptomatic/mild (60%),flu like (40%), mostly self limiting, can progess to chronic fibrocavitary disease or disseminated disease to any tissue/organ Recovery depends on T-lymphocyte response |
| other endemic mycoses | paracoccidioidomycosis (south american blastomycosis) acute/subacute (juvenile), chronic (adult, or opportunistic. Large yeast with multiple buds "ships wheel" |
| opportunistic fungal pathogens | monomorphic, acquired via inhalation, cause of disease in immunocompromised, same lab diagnosis as other fungi |
| immunocompromised and fungal infections | chemotherapy (aspergillus pneumocystis), assisted ventilation (aspergillus), malnutrition (pneumocystis, C. neoformans), HIV/AIDS (C. neoformans, pneumocystis), Neutropenia (aspergillus and others) |
| Cryptococcus neoformans | cryptococcosis, encapsulated yeast in tissue, unencapsulted in environment |
| epidemiology (cryptococcus) | worldwide distribution, grows well in soil enriched by pigeon droppings, most common fungal infection seen in AIDS |
| pathogenesis (cryptococcus) | inhalation of unencapsulated yeasts into alveoli triggers production of capsule (GXM, detectable in blood and fluids, down regulates the immune response), has strong affinity for CNS, can oxidize exogenous catecholamines to melanin |
| Pneumocystis Jiroveci | pneumocystis pneumonia, lacks ergosterol in cell wall, difficult to grow in culture |
| epidemiology (jiroveci) | worldwide, may or may not be person to person transmissible, low level of infectivity (need to be immunocompromised) |
| Aspergillus | Aspergillosis (fumigatus, flavus, niger) |
| epidemiology (aspergillus) | worldwide, found in decaying matter, soil, and air, causes allergic aspegillosis or invasive aspergillosis (fungal ball) |
| Hantavirus | hantavirus pulmonary syndrome, severe pulmonary distress, pneumonia, high mortality, ss- RNA, 3 segments (S,M,L), reservoir: long tailed pygmy rice rats (chile), rats and mice (US), infection by inhalation of excreta. Emerging. |
| Metapneumovirus | bronchiolitis, recently recognized, seems to be widespread, RT-PCR needed for diagnosis |
| otitis media | earache, fever, discharge, irritability, vomiting, diarrhea. Various bacterial causes |
| sinusitis | nasal congestion, purulent discharge, pain over affected area. Due to various bacteria |
| conjunctivitis | redness, discharge, irritation. Due to various viruses and bacteria |
| common cold | sneezing, rhinorrhea, blocked nose, mild sore throat, headache, malaise. Rhinoviruses and coronaviruses |
| Pharyngitis and tonsilitis | sore scratchy throat, exudate on tonsils. Adenoviruses, strep pyogenes |
| Laryngitis | symptoms of URTI plus hoarseness, usually viral |
| Diptheria | exudative pharyngitis, sore throat, low grade fever and malaise, pseudomembrane, C. diptheria |
| Acute bronchitis | symptoms of RTI, productive cough. Due to various organisms |
| Whooping cough | Cararrhal phase:rhinorrhea, sneezing, malaise, fever, anorexia. Paroxysmal phase:repetitive coughing with whoops, vomiting, leukocytosis. Due to B. pertussis |
| Croup | Mild upper RTI, fever, noisy respiration, barking. Due to HPIV |
| Bronchiolitis | fever, wheezing, tachypnea, rales. Due to RSV, HPIV |
| Influenza | fever, malaise, myalgia, sore throat, nonproductive cough, rhinorrhea, sneezing. Due to influenzaviruses |
| TB | fever, malaise, weight loss, night sweats, hemoptysis. Due to M. tuberculosis |
| Acute pneumonia | fever, general feeling of sickness, chest pain, cough, shortness of breath, rapid respiration, shadowy infiltrate on chest XRay. Due to various organisms |
| Chronic pneumonia | mild: fever and cough more severe: chills, malaise, fever, chest pain, sputum production, weight loss, granulomatous lesions. Due to endemic and opportunistic fungi |
Created by:
kamarsh
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